Combination Immunotherapy Effective in Treating Castration-Resistant Prostate Cancer

Checkpoint inhibitors plus myeloid-derived suppressor cell inhibitors show promise as prostate cancer treatment.

Findings from a new study reveal that combination immunotherapy may effectively treat advanced castration-resistant prostate cancer. A combination of checkpoint inhibitors and drugs that target immune cells may be the key to treating these patients.

Castration-resistant prostate cancer progresses despite androgen deprivation therapy, and can progress and metastasize if left untreated. Patients may undergo additional hormonal treatments, despite lack of evidence of survival benefit.

Corticosteroids, chemotherapy, and immunotherapy may all be used to treat castration-resistant prostate cancer. However, more effective treatment options are needed to prevent unnecessary costs and side effects that come with ineffective treatments.

In the study, which was published by Nature, the authors developed a chimeric mouse model to evaluate a combination of checkpoint inhibitors and treatments that target myeloid-derived suppressor cells (MDSCs). MCSCs are immune cells that have strong immunosuppressive abilities, and are involved with tumor creation and metastasis.

"A significant number of advanced prostate cancer patients treated with a chemical castration therapy called androgen deprivation therapy experience relapse with relentless progression to lethal metastatic, castration-resistant prostate cancer," said researcher Ronald DePinho, MD. "While immune checkpoint blockade therapy is effective in many cancers, it has been less successful for this particular form of prostate cancer, which has motivated a search for targeted therapies that overcome this resistance."

First, the authors tested CTLA4 and PD1 checkpoint inhibitors against the cancer. They found that the combination was only modestly effective.

MDSC inhibitors, such as cabozantinib and BEZ, were observed to be minimally effective, as well. However, a combination approach, including checkpoint and MDSC inhibitors, was extremely successful, according to the study.

"Strikingly, both primary and metastatic castration-resistant prostate cancer responded to a combined checkpoint blockade and MDSC targeted therapeutic approach," Dr DePinho said. "These observations in mouse models of prostate cancer, using a sophisticated genetic approach developed by James Horner at MD Anderson, illuminate a clinical path hypothesis for combining immune checkpoint blockades with MDSC-targeted therapies in the treatment of this aggressive cancer."

These findings suggest that the combination approach may successfully treat castration-resistant prostate cancer in humans, even if it has metastasized.

While the preliminary results are positive, the authors added that clinical trials are needed to explore the use of this combination treatment. Specifically, the future studies should include anti-androgen drugs for patients with castration-resistant and newly diagnosed cases of prostate cancers to achieve a durable clinical response, the study concluded.